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Non-genomic regulation of intermediate conductance potassium channels by aldosterone in human colonic crypt cells

Bowley, K.A., Morton, M.J., Hunter, M. and Sandle, G.I. (2003) Non-genomic regulation of intermediate conductance potassium channels by aldosterone in human colonic crypt cells. Gut, 52 (6). pp. 854-860. ISSN 0017-5749

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BACKGROUND: Aldosterone has a rapid, non-genomic, inhibitory effect on macroscopic basolateral K+ conductance in the human colon, reducing its capacity for Cl− secretion. The molecular identity of the K+ channels constituting this aldosterone inhibitable K+ conductance is unclear.

AIM: To characterise the K+ channel inhibited by aldosterone present in the basolateral membrane of human colonic crypt cells.

METHODS: Crypts were isolated from biopsies of healthy sigmoid colon obtained during colonoscopy. The effect of aldosterone on basolateral K+ channels, and the possible involvement of Na+:H+ exchange, were studied by patch clamp techniques. Total RNA from isolated crypts was subjected to reverse transcriptase-polymerase chain reaction (RT-PCR) using primers specific to intermediate conductance K+ channels (KCNN4) previously identified in other human tissues.

RESULTS: In cell attached patches, 1 nmol/l aldosterone significantly decreased the activity of intermediate conductance (27 pS) K+ channels by 31%, 53%, and 54% after 1, 5 and 10, minutes, respectively. Increasing aldosterone concentration to 10 nmol/l produced a further 56% decrease in channel activity after five minutes. Aldosterone 1–10 nmol/l had no effect on channel activity in the presence of 20 µmol/l ethylisopropylamiloride, an inhibitor of Na+:H+ exchange. RT-PCR identified KCNN4 mRNA, which is likely to encode the 27 pS K+ channel inhibited by aldosterone.

CONCLUSION: Intermediate conductance K+ channels (KCNN4) present in the basolateral membranes of human colonic crypt cells are a target for the non-genomic inhibitory effect of aldosterone, which involves stimulation of Na+:H+ exchange, thereby reducing the capacity of the colon for Cl− secretion.

Item Type: Article
Copyright, Publisher and Additional Information: Copyright © 2003 BMJ Publishing Group Ltd & British Society of Gastroenterology
Institution: The University of Leeds
Academic Units: The University of Leeds > Faculty of Biological Sciences (Leeds) > Institute of Membrane and Systems Biology (Leeds)
Depositing User: Milburn Gemma
Date Deposited: 13 Mar 2006
Last Modified: 21 Jun 2014 18:49
Published Version: http://gut.bmjjournals.com/cgi/content/full/52/6/8...
Status: Published
Refereed: Yes
Identification Number: 10.1136/gut.52.6.854
URI: http://eprints.whiterose.ac.uk/id/eprint/229

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